The proposed research is based on the long-term observation by pathologists, radiologists, and clinicians that hyaline cartilage is a unique connective tissue consisting of a uniform cell population residing in an extensive matrix without cell-cell interaction and that cartilage lacks nerves and a capillary blood supply, thus it can be referred to as an avascular tissue. Also, cartilage contrary to bone, is not or only very rarely invaded by neoplasms. It therefore represents a unique system to study both normal invasion (capillary penetration) as well as neoplastic invasive processes. In preliminary studies we were able to show that cartilage contains a tissue derived, low molecular weight cationic protein that acts as a potent mammalian collagenase inhibitor. Collagenases released by both normal and neoplastic cells can be inhibited by this protein. Isolated tumor cells (human osteosarcoma cells or human metastatic breast carcinoma cells) and endothelial cells (positive control) but not fibroblasts and smooth muscle cells (negative controls) are inhibited in culture by cartilage derived "cytotoxic factors" which contain the collagenase inhibitor. The proposed research intends to study and identify these cartilage derived "cytotoxic factors".